The C3b receptor of human erythrocytes (E), neutrophils, monocytes and B lymphocytes has recently been identified as a glycoprotein of 205,000 molecular weight that had been purified from E membranes 1600-fold and to homogeneity. This membrane glycoprotein was initially sought and characterized as a constituent of human E membrane that could impair activation of the alternative complement pathway by inducing loss of function of the amplification C3 convertase, C3b, Bb, through displacement of Bb from C3b and by promoting cleavage-inactivation of C3b by C3b inactivator. Monospecific rabbit antibody to this glycoprotein neutralized its inhibitory activities, blocked C3b receptor-dependent rosettes by the peripheral blood cells, bound specifically only to cells expressing C3b receptors, and immunoprecipitated only membrane proteins of 205,000 molecular weight from each of these cells that had been surface radioiodinated. The objectives of the proposed research relate to the inhibitory capacity of the C3b receptor in its membrane-associated form, to the topographic distribution of the receptor on cell membranes, to its role in receptor mediated endocytosis, to the fate of ligand that is internalized following binding to the receptor, to turnover of the receptor on monocytes under various conditions, to the transmembrane orientation of the receptor, to the definition of its oligomeric composition, to its association with other membrane proteins, and to alterations in systemic lupus erythematosus. These studies, in general, utilize established techniques and are made possible by monospecific anti-C3b receptor antibody to identify the receptor in membranes and complex mixtures of membrane proteins.